LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function

LARP4 interacts with NEMmRNAs. (A) Overview of enrichment analysis performed on eCLIP data sets for 150 RBPs in K562 and HepG2 cell lines. (B) Enrichment analysis for RNA-target set (eCLIP data) overlapping with mitochondrial genes. The significance of overlap (hypergeometric test) for each RBP data set is plotted on the y-axis and the number of overlapping targets is plotted on the x-axis. RBPs with significant overlap (P-value ≤ 0.05) and LARP4-K562 also shown (P-value = 0.06). (C) Enrichment analysis for RNA-target set (eCLIP data) overlapping with proteins in the KEGG OXPHOS pathway (HSA_00190). Only RBPs with statistically significant overlap (P-value ≤ 0.05, hypergeometric test) are shown. (D) Diagram showing the proportion of LARP4 eCLIP targets that encode mitochondrial proteins. (E–G) Metascape gene ontology (GO) analysis was performed on the three LARP4 eCLIP data sets from HEK293 (E), HepG2 (F), and K562 (G) cells. P-values are calculated by a hypergeometric test. (H,I) Comparison of mitochondrial enrichment scores from the APEX-seq atlas (Fazal et al. 2019) for LARP4 target and nontarget transcripts. eCLIP experiments were performed in independent biological duplicates for each cell line (N = 2). Gene-target lists of each eCLIP data set are defined as genes encoding an mRNA containing at least one peak that passes significance thresholds (−log₁₀[P-value] ≥ 7, Fisher's exact test; log₂[fold-change (IP/input)] ≥ 4). See also Supplemental Figure S1.